Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia.

Abstract

Mild hypoglycemia is common in clinical practice. Severe hypoglycemia results in heat shock protein and associate co-chaperone changes. Whether mild prolonged hypoglycemia elicits a similar response with inflammatory and oxidative-stress responses compared with a severe hypoglycemic event is unclear; therefore, this pilot exploratory study was undertaken. We performed a case-control induced hypoglycemia clamp study, maintaining blood glucose at 2.8 mmol/L (50 mg/dL) for 1 h in 17 subjects (T2D (n = 10); controls (n = 7)). Blood sampling was performed at baseline, hypoglycemia, and 24 h; slow off-rate modified aptamer (SOMA)-scan plasma protein analysis of HSP-related proteins, inflammatory stress markers, and oxidative stress markers was performed. In total, 16 HSPs were analyzed. At baseline, TLR4:MD-2 complex was elevated (p = 0.01), whilst HSPA8 was lower (p < 0.05) in T2D. At hypoglycemia, UBE2N, STIP1, and UBE2L3 increased (all p < 0.05), whilst TLR4:MD-2 and HSPA8 decreased (p < 0.05) in T2D versus baseline. In follow-up after hypoglycemia, HSPs normalized to baseline by 24 h, except UBE2L3 (p < 0.05), which was decreased in controls versus baseline. Correlation of altered inflammatory markers with HSPs revealed the following: at baseline, TLR4:MD-2 correlated with CXCL10 (p < 0.01) and SIGLEC1 (p < 0.05) in controls; HSPA8 negatively correlated with IL5 (p < 0.05) in T2D. A negative correlation between urinary isoprostane 8-iso PGF2α, a marker of oxidative stress, and HSPA1A was seen at 24 h in T2D only (p < 0.05). In conclusion, the HSP changes seen for mild prolonged hypoglycemia were similar to those previously reported for a severe event. However, mild prolonged hypoglycemia appeared to elicit an increased inflammatory response that was associated with heat shock and related proteins.

• Authors: Abu Saleh Md Moin, Manjula Nandakumar, Hassan Kahal, Thozhukat Sathyapalan, Stephen L Atkin, Alexandra E Butler
• Journal: Cells (Cells) Vol. 10 Issue 11 (11 10 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34831332 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Biomarkers
• Heat-Shock Proteins
• Proteins
• 8-epi-prostaglandin F2alpha
• Dinoprost
• UBE2L3 protein, human
• Ubiquitin-Conjugating Enzymes

Topics

• Adult
• Biomarkers (metabolism)
• Case-Control Studies
• Diabetes Mellitus, Type 2 (blood, metabolism)
• Dinoprost (analogs & derivatives, metabolism)
• Female
• Heat-Shock Proteins (blood)
• Heat-Shock Response
• Humans
• Hypoglycemia (blood, metabolism)
• Inflammation (metabolism)
• Male
• Middle Aged
• Oxidative Stress
• Protein Interaction Mapping
• Proteins (metabolism)
• Ubiquitin-Conjugating Enzymes (metabolism)